The effect of ethanol and nicotine on ER stress in human placental villous explants.

Pregnant mothers continue smoking and drinking during pregnancy. To clarify the mechanisms of nicotine and ethanol toxicity during development, we have examined their effects on endoplasmic reticulum (ER) stress in human first trimester and term placental explants. First trimester and term human placental explants were treated with ethanol (2 ‰) or nicotine (15 µM), or their combination. The ER stress markers glucose regulated protein 78 (GRP78/BiP) and inositol requiring enzyme 1 α (IRE1α) were analyzed by immunoblotting. A statistically significant increase (p < 0.05) of GRP78/BiP by nicotine was noted in first trimester placental explants at 48 h, and in term placental explants at 24 h. Ethanol did not change protein expression of GRP78/BiP in either first trimester or term placental explants. IRE1α increased, although not statistically significantly, by all treatments in both first trimester and term placental explants. Thus, regardless of the known structural and functional differences in early and late placenta, both responded very similarly to the toxic compounds studied. These data support our earlier results in BeWo cells (Repo et al., 2014) implicating that nicotine induces ER stress in human placenta and may interfere with placental functions potentially disrupting fetal growth and development.

Reliability and Validity of The Finnish Version of The Boston Carpal Tunnel Questionnaire among Surgically Treated Carpal Tunnel Syndrome Patients.

BACKGROUND AND AIMS: The Boston Carpal Tunnel Questionnaire is the most commonly used outcome measure in the assessment of carpal tunnel syndrome. The purpose of this study was to translate the original Boston Carpal Tunnel Questionnaire into Finnish and validate its psychometric properties. MATERIALS AND METHODS: We translated and culturally adapted the Boston Carpal Tunnel Questionnaire into Finnish. Subsequently, 193 patients completed the Finnish version of the Boston Carpal Tunnel Questionnaire, 6-Item CTS Symptoms Scale, and EuroQol 5 Dimensions 12 months after carpal tunnel release. The Boston Carpal Tunnel Questionnaire was re-administered after a 2-week interval. We calculated construct validity, internal consistency, test-retest reliability, and coefficient of repeatability. We also examined floor and ceiling effects. RESULTS: The cross-cultural adaptation required only minor modifications to the questions. Both subscales of the Boston Carpal Tunnel Questionnaire (Symptom Severity Scale and Functional Status Scale) correlated significantly with the CTS-6 and EuroQol 5 Dimensions, indicating good construct validity. The Cronbach's alpha was 0.93 for both the Symptom Severity Scale and Functional Status Scale, indicating high internal consistency. Test-retest reliability was excellent, with an intraclass correlation coefficient greater than 0.8 for both scales. The coefficient of repeatability was 0.80 for the Symptom Severity Scale and 0.68 for the Functional Status Scale. We observed a floor effect in the Functional Status Scale in 28% of participants. CONCLUSION: Our study shows that the present Finnish version of the Boston Carpal Tunnel Questionnaire is reliable and valid for the evaluation of symptom severity and functional status among surgically treated carpal tunnel syndrome patients. However, owing to the floor effect, the Functional Status Score may have limited ability to detect differences in patients with good post-operative outcomes.

Cross-Cultural Adaptation and Validation of the Finnish Version of the Michigan Hand Outcomes Questionnaire.

BACKGROUND AND AIMS: Michigan Hand Outcomes Questionnaire is a widely used patient-reported outcome measure in hand surgery. The aim of this study was to translate and validate the Michigan Hand Outcomes Questionnaire into Finnish for Finnish patients with hand problems following international standards and guidelines. MATERIAL AND METHODS: The original English Michigan Hand Outcomes Questionnaire was translated into Finnish. Altogether, 115 patients completed the Finnish Michigan Hand Outcomes Questionnaire, and reference outcomes: Disabilities of the Arm and Shoulder, EQ-5D 3L and pain intensity on a visual analog scale. Grip and key pinch forces were measured. After 1-2 weeks, 63 patients completed the Finnish Michigan Hand Outcomes Questionnaire the second time. The Michigan Hand Outcomes Questionnaire was analyzed for internal consistency, repeatability, correlations with the reference outcomes, and factor analysis. RESULTS: Cronbach's alpha ranged from 0.90 to 0.97 in all the Michigan Hand Outcomes Questionnaire subscales, showing high internal consistency. The intraclass correlation coefficient showed good to excellent test-retest reliability ranging from 0.66 to 0.91 in all the Michigan Hand Outcomes Questionnaire subscales. In factor analysis, the structure with six subscales was not confirmed. All the subscales correlated with Disabilities of the Arm and Shoulder score, and five subscales correlated with EQ-5D index. CONCLUSION: The Finnish version of the Michigan Hand Outcomes Questionnaire showed similar properties compared to the original English version and thus can be used as patient-reported outcome measure for Finnish patients with hand problems.

Health-related quality of life after oncological resection and reconstruction of the chest wall.

OBJECTIVES: There is limited information of the health-related quality of life (HRQoL) after surgical treatment of chest wall tumors. This cross-sectional study aimed to assess long-term HRQoL after chest wall reconstruction following oncological resection. METHODS: Seventy-eight patients having undergone chest wall tumor resection and reconstruction during 1997-2015 were invited to complete the 15D and QLQ-C30 HRQoL instruments. RESULTS: Altogether, 55 patients (17 men and 38 women), with a mean (SD) age of 68 (14) years, completed the questionnaires (response rate 71%). Patients had been operated due to soft tissue sarcoma (n = 16), advanced breast cancer (n = 15), osteo- or chondrosarcoma (n = 14), or other tumor (n = 10). Median time after primary surgery was 66 (IQR 38, 141) months. The resection was full thickness in 29/55 cases and partial thickness in 26/55 cases. Chest wall reconstruction was required for 47/55 cases (85%). Reconstruction was performed using soft-tissue flap in eight cases, skeletal stabilizations with mesh or mesh-cement-mesh (sandwich method) in 15 cases, and skeletal stabilizations and soft-tissue flap in 24 cases. Patients' mean 15D score (0.878, SD 0.111) was comparable to that of the age- and gender-standardized general population (0.891, SD 0.041). Limitations in breathing and usual activities were noted. The QLQ-C30 cancer-specific HRQoL was 72 points (maximum 100). Scores in the QLQ-C30 Functional scales ranged from 78 (Physical) to 91 (Social). CONCLUSIONS: Long-term HRQoL in patients after chest wall reconstruction following oncological resection is fair and comparable to that of the general population. Limitations in breathing and usual activities can occur.

Validation of the Finnish version of the BODY-Q patient-reported outcome instrument among patients who underwent abdominoplasty.

BACKGROUND: Massive weight loss can notably affect patients' health-related quality of life (HRQoL) and body image. Yet, no body contouring specific instruments to assess HRQoL and body image after massive weight loss have been validated in Finnish. The BODY-Q includes 26 independently functioning scales and a single checklist that measure appearance, HRQoL, and experience of care. The aim of the present study was to translate and validate a Finnish version of the BODY-Q among patients who underwent abdominoplasty. METHODS: The BODY-Q was translated into Finnish using recommended guidelines. Eighty-two patients who underwent abdominoplasty due to massive weight loss were identified from hospital records using procedure codes. A postal survey including the BODY-Q, the 15D, and general health and pain instruments was used. Criterion validity, Cronbach's alpha, and floor and ceiling effects were analyzed. RESULTS: The BODY-Q translated well into Finnish. Fifty-three patients returned the questionnaires (response rate 65%) and were included. All but the Scars subscale correlated significantly with the 15D mean score, thus indicating strong criterion validity against a generic HRQoL tool. The Excess Skin and the Physical Function scales reached the ceiling effect (>15% of maximum points) in our postoperative sample. No floor effects were observed. Internal consistency of the BODY-Q scales was high (Cronbach's alpha range, 0.81-0.95). CONCLUSIONS: The Finnish version of the BODY-Q instrument is equivalent in terms of content, accuracy, and comprehensiveness to the original English version. The findings of the present study indicate that the BODY-Q has psychometric properties suitable for assessing outcomes and treatment effectiveness of abdominoplasty.

Functional Outcome After Lower Extremity Soft Tissue Sarcoma Treatment: A Pilot Study Based on Translated and Culturally Adapted Measures.

BACKGROUND AND AIMS: The present standard of care in treating lower extremity soft tissue sarcomas is function-sparing, limb-preserving resection and reconstruction with or without oncological therapy. The aim of this pilot study was to test the suitability and adequacy of the Finnish translations of two functional outcome questionnaires (Toronto Extremity Salvage Score and Musculoskeletal Tumor Society score) and to perform a preliminary investigation of functional outcomes of Finnish lower-limb soft tissue sarcoma patients after operative treatment. MATERIALS AND METHODS: Between June 2015 and December 2015, consecutive surgically treated outpatients were asked to participate in the study. Demographic, clinical, surgical, and oncological outcome data were collected. Two functional outcome questionnaires were used (Toronto Extremity Salvage Score and Musculoskeletal Tumor Society scores). A comparative analysis is presented. RESULTS: A total of 19 lower-limb soft tissue sarcoma patients with a mean follow-up time of 2 years and 10 months were included. All (n = 19) invited patients participated in the study. Mean age was 62.3 years. In total, 13 had high-grade sarcomas. Eight wounds were closed directly, four used skin grafts, and five required flap reconstructions. One patient required a tumor prosthesis, and one required a rotationplasty. A total of 14 patients received oncological therapy. No problems or difficulties were reported in using and completing the Finnish versions of the Toronto Extremity Salvage Score or Musculoskeletal Tumor Society questionnaires. The overall Toronto Extremity Salvage Score and Musculoskeletal Tumor Society scores were 88 and 76, respectively. CONCLUSION: This pilot study suggests that the Finnish versions of the Toronto Extremity Salvage Score and Musculoskeletal Tumor Society questionnaires are suitable for measuring functional outcome after lower extremity soft tissue sarcomas treatment. Functional outcomes vary from moderate to excellent.

Treatment of compound tibia fracture with microvascular latissimus dorsi flap and the Ilizarov technique: A cross-sectional study of long-term outcomes.

BACKGROUND: Extensive compound tibial fractures present reconstructive challenges. The present study aimed to assess the outcomes of microvascular latissimus dorsi (LD) flap combined with the Ilizarov technique for extensive compound tibial fractures with bone loss and bone healing complications. METHODS: Patient records were reviewed retrospectively. The Lower Extremity Functional Scale (LEFS), the Disabilities of the Arm, Hand and Shoulder (DASH), and the 15D health-related quality of life (HRQoL) instrument were applied. RESULTS: Between 1989 and 2014, 16 patients underwent reconstruction with a microvascular LD flap and bone transport (11/16) or late bone lengthening (5/16). The mean clinical follow-up time was 6.6 (standard deviation (SD): 6.5) years. Three patients had minor complications requiring reoperation. Partial necrosis of one flap required late flap reconstruction in one case. Late bone grafting was used to enhance union in eight of 16 cases. The mean new bone gain was 3.8 cm (SD: 2.5). Overall, 11 patients completed the questionnaires in a mean of 22.3 years (SD: 2.4) after surgery. The main findings revealed a relatively good function of the reconstructed limb and good shoulder function. The mean HRQoL was comparable to that of an age-standardized sample of the general population. CONCLUSION: Segmental tibia transport and lengthening to correct limb length discrepancy do not compromise the microvascular muscle flap. Combined microvascular LD flap reconstruction and the Ilizarov technique can be used in treating acute compound tibial defects, pseudoarthrosis, and osteitis, all associated with significant amputation risk. Fair long-term functional outcomes and HRQoL are achieved when these combined techniques are used.

Criteria and challenges of the human placental perfusion ­ Data from a large series of perfusions.

Perfusion of human placental cotyledon has been used extensively to study transplacental transfer of endogenous and exogenous compounds. However, many challenges in the use of the method exist, including availability of placentas and complexity of the method itself. In Kuopio, Finland we have carried out human placental perfusions since 2005 using the same method with data now from over one hundred perfusions. This has allowed us to study whether the way of delivery, placental weight, and/or the length of pregnancy affect the two major criteria of a successful perfusion: volume loss (leak) from fetal to maternal circulation, and transplacental transfer of the reference compound antipyrine. The only statistically significant result was the reduction of the fetomaternal ratio of antipyrine by the placental age over 40 weeks (p=0.0004). The success criteria were not affected by the weight of the placenta or the way of delivery. There was no effect by the antipyrine concentration on antipyrine transfer. In vitro incubation with different concentrations of study compounds and different tubing materials could offer an easy way to study potentially reduced recovery due to binding to perfusion system.

Paricalcitol aggravates perivascular fibrosis in rats with renal insufficiency and low calcitriol.

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.

Recurrent opioid toxicity after pre-hospital care of presumed heroin overdose patients.

BACKGROUND: In patients with presumed heroin overdose, the recommended time of observation after reversing heroin toxicity with naloxone varies widely. The aims of this study were to examine the incidence of recurrent opioid toxicity and the time interval in which it occurs after pre-hospital treatment in presumed heroin overdose patients. METHODS: We undertook a retrospective study in Helsinki (population, 560,000). Records were reviewed from 1 January 1995 to 31 December 2000. Patients included were treated by the emergency medical service (EMS) for a presumed heroin overdose. Patients with known polydrug/alcohol use or the use of opioids other than heroin were excluded. The EMS records were compared with the cardiac arrest database and the medical examiners' records. RESULTS: One hundred and forty-five patients were included. The median dose of pre-hospital administered naloxone was 0.4 mg. After pre-hospital care, 84 patients refused further care and were not transported to an emergency department (ED). Seventy-one received pre-hospital naloxone, and no life-threatening events were recorded during a 12-h follow-up period in these patients. After pre-hospital care, 61 patients were transported to an ED. Twelve patients received naloxone in the ED for respiratory depression. All had signs of heroin use-related adverse events within 1 h after receiving pre-hospital naloxone. CONCLUSIONS: Allowing presumed heroin overdose patients to sign out after pre-hospital care with naloxone is safe. If transported to an ED, a 1-h observation period after naloxone administration seems to be adequate for recurrent heroin toxicity.

Outcome after heroin overdose and cardiopulmonary resuscitation.

BACKGROUND: The survival of heroin overdose patients resuscitated from cardiac arrest is reported to be poor. The aim of our study was to investigate the outcome and characteristics of survivors after cardiac arrest caused by heroin overdose. METHODS: This was a retrospective study in a medium-sized city (population, 560,000). Between 1 January 1997 and 31 December 2000, there were 94 combined cardiac arrests caused by acute drug poisonings. The main outcome measure was survival to discharge. RESULTS: Cardiopulmonary resuscitation was attempted in 19 heroin overdose patients (group A) and in 53 patients with cardiac arrest caused by other poisonings (group B). Three (16%) vs. six (11%) patients were discharged alive (group A vs. B, respectively). The survivors in group A had an Emergency Medical Service (EMS)-witnessed cardiac arrest or the Emergency Dispatching Centre was called before the arrest occurred. There was no statistically significant difference between the two groups in terms of survival. Survivors in both groups suffered from acute renal failure (two), hypoglycaemia (four) and hypothermia (three). CONCLUSION: Survival after cardiac arrest caused by heroin overdose is possible if the arrest is EMS witnessed or the Emergency Dispatching Centre is called before the cardiac arrest occurs. In comparison with cardiac arrests caused by other poisonings, there was no difference in survival. The incidence and mechanism of hypoglycaemia should be examined in further studies.

The use of undiluted amiodarone in the management of out-of-hospital cardiac arrest.

INTRODUCTION: The Resuscitation 2000 Guidelines recommends amiodarone as the antiarrhythmic drug of choice in treatment of resistant ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). Amiodarone has been associated with side-effects and difficulty of administration, due to recommended dilution, rendering it suboptimal for out-of-hospital cardiac arrest (CA) management. In the present study we report experiences and side-effects of the use of undiluted amiodarone in CA management in Helsinki Emergency Medical Service (EMS) during a 2-year period. METHODS: On October 1, the Resuscitation 2000 Guidelines were put into practice in Helsinki EMS. Thus, in the cardiac arrest treatment protocol, after three ineffective shocks and 1 mg of adrenaline (epinephrine), a bolus of 300 mg of undiluted amiodarone (Cordarone 50 mg ml(-1), Sanofi-Synthelabo, Helsinki, Finland) was administered into a vein located as centrally as possible. The Helsinki EMS performs systematic data collection according to the Utstein Guidelines. The blood pressure levels, heart rates and the need for vasopressors, of the patients with sustained return of spontaneous circulation (ROSC), were collected from the ambulance charts. RESULTS: During October 1, 2000 and September 30, 2002, 712 patients were considered for resuscitation and 566 were resuscitated. The initial rhythms were as follows: 32% had VF/VT, 36% had asystole and 32% had pulseless electrical activity (PEA). Of the 180 patients with VF/VT, 75 (42%) received undiluted amiodarone in addition to other resuscitative measures. Of the patients with asystole or PEA, 12 (6%) and 18 (10%), respectively, received amiodarone. The blood pressure levels and the need vasopressors after ROSC and during transportation to the hospital were similar among the patients who received and those who did not receive amiodarone. CONCLUSIONS: The present study suggests that amiodarone can be administered undiluted without unmanageable haemodynamical side-effects in the treatment of out-of-hospital cardiac arrest. This is likely to save time and simplifies the treatment protocol in the prehospital setting.

The incidence of out-of-hospital ventricular fibrillation in Helsinki, Finland, from 1994 to 1999.

Early defibrillation by emergency medical services has been a success story in the treatment of ventricular fibrillation. This success has been followed by recommendations to allow public access to defibrillation equipment. We tracked the changes in incidence of ventricular fibrillation from prospectively collected data from the Helsinki Cardiac Arrest Register. We found that the incidence of out-of-hospital ventricular fibrillation of cardiac origin fell by 48% from 1994 to 1999 (p=0.0036). The primary and secondary prevention of coronary artery disease may not be the only reasons for this change and so new public-access defibrillation programmes should be delayed until our findings are confirmed.

Cardiac arrests witnessed by EMS personnel in a multitiered system: epidemiology and outcome.

The purpose of the study was to determine the epidemiology and the etiology of cardiac arrests witnessed by emergency medical services (EMS) personnel and the survival from resuscitation according to the Utstein style. Consecutive prehospital cardiac arrests witnessed by EMS personnel in the Helsinki City EMS system between January 1, 1994 and December 31, 1995 were included in this prospective cohort study. A total of 809 cardiac arrests were registered during the study period, 108 (13.3%) of which were EMS-witnessed. The incidence of EMS-witnessed cardiac arrests was 1.8 per 1,000 urgent calls per year. Resuscitation was attempted in 94 patients, 45 of whom (47.9%) were hospitalized alive and 15 of whom (16.0%) were discharged. Fourteen of the survivors were discharged with overall performance category I or II. Cardiac etiology was verified in 60 (55.6%) cases. In multivariate analysis, initial rhythm of ventricular fibrillation and cardiac etiology remained independent factors of survival. These results indicate that overall survival rates in EMS-witnessed cardiac arrests have remained low but those who survive are discharged without major neurological sequelae. Noncardiac etiology accounts for 45% of cases and seems to be a major determinant of low overall survival rates.